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NM_001100.4(ACTA1):c.986_989dup (p.Lys330fs) AND Actin accumulation myopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 5, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002828164.3

Allele description [Variation Report for NM_001100.4(ACTA1):c.986_989dup (p.Lys330fs)]

NM_001100.4(ACTA1):c.986_989dup (p.Lys330fs)

Gene:
ACTA1:actin alpha 1, skeletal muscle [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
1q42.13
Genomic location:
Preferred name:
NM_001100.4(ACTA1):c.986_989dup (p.Lys330fs)
HGVS:
  • NC_000001.11:g.229431723_229431726dup
  • NG_006672.1:g.7372_7375dup
  • NG_093759.1:g.728_731dup
  • NG_093760.1:g.108_111dup
  • NM_001100.4:c.986_989dupMANE SELECT
  • NP_001091.1:p.Lys330Asnfs
  • NP_001091.1:p.Lys330fs
  • LRG_429t1:c.985_988dup
  • LRG_429:g.7372_7375dup
  • LRG_429p1:p.Lys330Asnfs
  • NC_000001.10:g.229567468_229567469insTTGA
  • NC_000001.10:g.229567470_229567473dup
  • NM_001100.3:c.985_988dup
Protein change:
K330fs
Molecular consequence:
  • NM_001100.4:c.986_989dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Actin accumulation myopathy (CMYO2A)
Synonyms:
Nemaline myopathy caused by mutation in the alpha-actin gene; CONGENITAL MYOPATHY 2A, TYPICAL, AUTOSOMAL DOMINANT; Myopathy, actin, congenital, with cores; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008070; MedGen: C3711389; OMIM: 161800

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003204029Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Oct 5, 2022)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Nemaline myopathy caused by absence of alpha-skeletal muscle actin.

Nowak KJ, Sewry CA, Navarro C, Squier W, Reina C, Ricoy JR, Jayawant SS, Childs AM, Dobbie JA, Appleton RE, Mountford RC, Walker KR, Clement S, Barois A, Muntoni F, Romero NB, Laing NG.

Ann Neurol. 2007 Feb;61(2):175-84.

PubMed [citation]
PMID:
17187373

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003204029.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the C-terminus of the ACTA1 protein. Other variant(s) that disrupt this region (p.Tyr364*) have been observed in individuals with ACTA1-related conditions (PMID: 17187373). This suggests that this may be a clinically significant region of the protein. This variant has not been reported in the literature in individuals affected with ACTA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the ACTA1 gene (p.Lys330Asnfs*72). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acid(s) of the ACTA1 protein and extend the protein by 23 additional amino acid residues.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024